Screening for cancer: are biomarkers of value?

– February/March 2011 8 Tumour markers
a 5-year survival rate of >90% can be
achieved when disease is confined to the
ovary. Unfortunately, only about 25% of
ovarian cancers are detected at this early
stage. This correlation between 5-year survival
rates and stage at diagnosis suggests
that screening and early detection may
improve outcome.
Because of its relatively low prevalence, a
screening strategy for ovarian cancer must
have an extremely high specificity to minimise
the number of false-positive results.
Based on a prevalence of 40 cases per
100,000 women, it has been estimated that
in order to achieve an acceptable positive
predictive value (at least 10%), an ovarian
cancer screening strategy should have a
specificity of 99.6% [14].
The main screening tests undergoing evaluation
for ovarian cancer are CA 125 and
transvaginal ultrasound (TVS). Currently,
two large prospective trials are evaluating
these modalities in screening healthy
women for ovarian cancer, namely the
PLCO study in the US [15] and the United
Kingdom Collaborative Trial of Ovarian
Cancer Screening (UKCTOCS) [16].
Preliminary results from the UK trial are
promising. Thus, of the 58 cancers detected
with CA 125 and TVS, 28 (48%) were
found to be either stage I or II. Sensitivity,
specificity and PPV of the two tests for
primary and tubal malignancies combined
were respectively 89.4%, 99.8% and 35.1%.
Currently, it is unclear whether screening
with CA 125 and TVS reduces mortality
from ovarian cancer [16]. Guidelines
therefore recommend against the use of
CA 125 either alone or in combination
with TVS in screening for ovarian cancer
in asymptomatic average-risk women outside
the context of a randomised controlled
trial [6,17].
HCG in screening for gestational
tropohoblastic neoplasia
Gestational trophoblastic neoplasia (GTN)
is a rare malignancy that originates from
placental tissue. Although most GTNs
develop following a molar pregnancy, they
can occur after any antecedent pregnancy.
As previously pointed out [3,18], the use of
human chorionic gonadotropin (HCG) to
screen for GTN in patients diagnosed with
a hydatidiform mole approaches the ideal
use of a screening biomarker as:
• HCG levels are increased in almost all
patients with trophoblastic disease,
• HCG is a highly sensitive marker for
small volume trophoblastic disease,
• The prevalence of malignant trophoblastic
disease in women diagnosed with a previous
hydatidiform mole is relatively high
(3 to 15%) and
• Effective chemotherapy is available for
malignant trophoblastic disease.
The combination of HCG measurements,
organised follow-up and availability of
effective chemotherapy means that GTN
is one of a few human malignancies that is
curable, even in advanced stages of the disease.
Indeed, cure rates for this malignancy
now approach 100%. An important practical
point in measuring HCG in GTN is that the
assay used should detect all the main forms
of the protein, especially the beta subunit.
Conclusion
Although the measurement of biomarkers
has great appeal for cancer screening,
their use to date has been disappointing
from the point of view of reducing mortality
from cancer, especially in asymptomatic
populations. Their main utility in screening
is likely to be in high-risk populations,
where the prevalence of cancer is high. A
good example of this is the use of HCG in
screening for GTN in patients who had a
previous diagnosis of a hydatidiform mole.
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The author
Michael J Duffy
Dept of Pathology and Laboratory
Medicine
St Vincent’s University Hospital, Dublin 4,
UCD School of Medicine and Medical Science,
University College Dublin, Dublin 4, Ireland.
Corresponding address:
Professor M J Duffy
Dept of Pathology and Laboratory
Medicine
St Vincent’s University Hospital
Elm Park, Dublin 4, Ireland.
Tel. +353-1-2094378
e-mail: michael.j.duffy@ucd.ie
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